Protein synthesis is a fundamental requirement for the development of an organism. The malaria parasite, Plasmodium, is unique in having a low copy number of nuclear-encoded, dispersed rRNA genes which are developmentally regulated. For a number of Plasmodium species, an A-type 18S rRNA has been shown to be expressed in asexual(blood) stages while an S-type rRNA is expressed in purified sporozoites isolated from salivary glands of infected mosquitoes. The expression of distinct rRNAs suggest that changing the central catalytic component of the ribosome, the rRNA, is a trigger for development. We are presently investigating both transcriptional control of the distinct rRNA genes and putative functional differences between the rRNAs, as these would be targets for intervention in the life cycle of the parasite through drug interaction. To further these studies, we have recently described the accumulation of mutations in rDNA units both within a clonal line of the human malaria parasite, P. falciparum, and between geographically distinct strains of the parasite. Also, the complete set of 18S-5S-28S genes from P. falciparum have been characterized from both the asexually expressed and sporozoite-expressed genes. This has enabled a detailed structural comparison of the secondary structures for the rRNAs corresponding to these genes. Interestingly, the sporozoite-expressed 28S rRNA shows differences in the site for stimulation of GTP hydrolysis in a manner that may be predicted to modulate its catalytic activity. Hydrolysis of GTP is a key regulatory step in other systems and therefore we predict that alteration of the site may trigger the development of the parasite. The effect of changes in the GTPase site are currently being investigated in vivo, by gene replacement in S. cerevisiae, and in vitro by transcription of synthetic genes with T7 RNA polymerase.